ID PROC_RABIT Reviewed; 458 AA.
AC Q28661;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JAN-2024, entry version 147.
DE RecName: Full=Vitamin K-dependent protein C;
DE EC=3.4.21.69;
DE AltName: Full=Anticoagulant protein C;
DE AltName: Full=Autoprothrombin IIA;
DE AltName: Full=Blood coagulation factor XIV;
DE Contains:
DE RecName: Full=Vitamin K-dependent protein C light chain;
DE Contains:
DE RecName: Full=Vitamin K-dependent protein C heavy chain;
DE Contains:
DE RecName: Full=Activation peptide;
DE Flags: Precursor; Fragment;
GN Name=PROC;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Shen L., He X., Dahlback B.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Protein C is a vitamin K-dependent serine protease that
CC regulates blood coagulation by inactivating factors Va and VIIIa in the
CC presence of calcium ions and phospholipids. Exerts a protective effect
CC on the endothelial cell barrier function.
CC {ECO:0000250|UniProtKB:P04070}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Degradation of blood coagulation factors Va and VIIIa.;
CC EC=3.4.21.69;
CC -!- SUBUNIT: Synthesized as a single chain precursor, which is cleaved into
CC a light chain and a heavy chain held together by a disulfide bond. The
CC enzyme is then activated by thrombin, which cleaves a tetradecapeptide
CC from the amino end of the heavy chain; this reaction, which occurs at
CC the surface of endothelial cells, is strongly promoted by
CC thrombomodulin.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P04070}. Golgi
CC apparatus {ECO:0000250|UniProtKB:P04070}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P04070}.
CC -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver.
CC -!- PTM: The vitamin K-dependent, enzymatic carboxylation of some Glu
CC residues allows the modified protein to bind calcium.
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate
CC and asparagine is (R) stereospecific within EGF domains. {ECO:0000250}.
CC -!- MISCELLANEOUS: Calcium also binds, with stronger affinity to another
CC site, beyond the GLA domain. This GLA-independent binding site is
CC necessary for the recognition of the thrombin-thrombomodulin complex.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; U49933; AAA92956.1; -; mRNA.
DR AlphaFoldDB; Q28661; -.
DR SMR; Q28661; -.
DR STRING; 9986.ENSOCUP00000041616; -.
DR MEROPS; S01.218; -.
DR GlyCosmos; Q28661; 3 sites, No reported glycans.
DR PaxDb; 9986-ENSOCUP00000013608; -.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR InParanoid; Q28661; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0050819; P:negative regulation of coagulation; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:1903142; P:positive regulation of establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1.
DR Gene3D; 2.10.25.10; Laminin; 2.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR012224; Pept_S1A_FX.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24278; COAGULATION FACTOR; 1.
DR PANTHER; PTHR24278:SF0; VITAMIN K-DEPENDENT PROTEIN C; 1.
DR Pfam; PF14670; FXa_inhibition; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001143; Factor_X; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF57196; EGF/Laminin; 2.
DR SUPFAM; SSF57630; GLA-domain; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript level;
KW Blood coagulation; Calcium; Cleavage on pair of basic residues;
KW Disulfide bond; EGF-like domain; Endoplasmic reticulum;
KW Gamma-carboxyglutamic acid; Glycoprotein; Golgi apparatus; Hemostasis;
KW Hydrolase; Hydroxylation; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL <1..27
FT /evidence="ECO:0000250"
FT PROPEP 28..36
FT /evidence="ECO:0000250"
FT /id="PRO_0000028122"
FT CHAIN 37..458
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028123"
FT CHAIN 37..192
FT /note="Vitamin K-dependent protein C light chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028124"
FT CHAIN 195..458
FT /note="Vitamin K-dependent protein C heavy chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028125"
FT PEPTIDE 195..209
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028126"
FT DOMAIN 37..82
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 91..126
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 130..170
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 210..447
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 250
FT /note="Charge relay system"
FT ACT_SITE 296
FT /note="Charge relay system"
FT ACT_SITE 399
FT /note="Charge relay system"
FT SITE 209..210
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT MOD_RES 42
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 43
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 50
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 52
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 55
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 61
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 62
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 65
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 107
FT /note="(3R)-3-hydroxyaspartate"
FT /evidence="ECO:0000250"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..58
FT /evidence="ECO:0000250"
FT DISULFID 86..105
FT /evidence="ECO:0000250"
FT DISULFID 95..100
FT /evidence="ECO:0000250"
FT DISULFID 99..114
FT /evidence="ECO:0000250"
FT DISULFID 116..125
FT /evidence="ECO:0000250"
FT DISULFID 134..145
FT /evidence="ECO:0000250"
FT DISULFID 141..154
FT /evidence="ECO:0000250"
FT DISULFID 156..169
FT /evidence="ECO:0000250"
FT DISULFID 177..316
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00463"
FT DISULFID 235..251
FT /evidence="ECO:0000250"
FT DISULFID 370..384
FT /evidence="ECO:0000250"
FT DISULFID 395..423
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 458 AA; 51088 MW; D75A5F990C8F29D7 CRC64;
IPDDVGYRNQ KTASKEGVCV VSKCQDGPNT LPRAKRANSF LEELRPSSLE RECVEEVCDL
EEAKEIFQSV DDTLAFWYKY VDGDQCAALP SEHPCSSQCC GHGTCADSIG GFSCQCHGGW
EGSFCQYEVR FSNCSVDNGG CAHYCLEEEA GRSCSCAPGY ELADDHLQCE PAVRFPCGRL
GWKRIEKKRG NVKRDLEQVD EMDEVDPRLI DGKLTRRGDS PWQVILLDSK KKLACGAVLI
HVSWVLTAAH CMEEPKKLFV RLGEYDLRRK ERWELDLNIQ EVLIHPNYSR STTDNDIALL
RLAQPATLSQ TIVPICLPDN GLAERELMQA GQETVVTGWG YHSSREKEAK RNRTFILNFI
TVPVAPQNEC EQVMSNIISE NMLCAGILGD RRDACDGDSG GPMVASFRGT WFLVGLVSWG
EGCGDLNNYG VYTKVSRYLD WIHSHIEEKE AAPESPAP
//
